The Strong Heart Study sought to estimate cardiovascular disease mortality and morbidity among Native Americans in relation to the general United States population. They reported that cardiovascular disease mortality rates in the Native American populations in Arizona were similar to the US averages (Lee et al., 1998). The prevalence of hypertension in most races (reported by American Heart Association, 2018: non- Hispanic white, non-Hispanic black, Mexican American) has generally increased over the past few decades (Benjamin et al., 2018). One group remains unreported or underreported?Native Americans?underscoring the importance of research in this area. Hypertension is one of the most modifiable and controllable risk factors for cardiovascular disease; however, the etiology of the development of hypertension may vary between racial groups. This may modify successful prevention and treatment strategies in these groups. Hyperinsulinemia in Native American populations has been consistently reported in the literature and is hypothesized for the current study to precede the development of: 1) endothelial dysfunction and 2) blood pressure (BP) dysregulation in this group. It has been demonstrated that Pima Indians regulate BP differently than their Caucasian counterparts. Pima Indians had higher fasting insulin concentrations, despite a normal oral glucose tolerance test. Hyperinsulinemia has also been associated with markers endothelial dysfunction. Thus, it is possible that high insulin concentration concomitantly targets two pathways associated with the increased risk for hypertension and cardiovascular events in this population. The Native American population is difficult to assess in a research setting due to historical reasons. However, the Hispanic population in our region in AZ has been reported to possess high levels of Native American ancestry (NAA) (range 7-75%) and may serve as a surrogate population. The purpose of this study is to quantify insulin status in Hispanics of varying proportions of NAA to determine its role in endothelial function and BP regulation. We hypothesize that Hispanics with higher proportions of NAA will: 1) possess higher insulin concentrations than those with lower proportions of NAA; 2) demonstrate impaired endothelial function; and 3) demonstrate greater BP reactivity to hypertensive stimuli. This 3-yr project will assess NAA, anthropometric measurements, insulin status, blood markers, blood vessel function, and BP responses. The team includes a Co-I with expertise in DNA admixture analysis, a physician, an endocrinologist, a statistician, and graduate and undergraduate students. The results will provide insight into the race-specific differences in the development of BP dysregulation and will inform future treatment strategies. We surmise that effective treatment will need to target glucose handling early to stop the downstream cascade leading to dysregulation.